دورية أكاديمية
Colorectal cancer-associated anaerobic bacteria proliferate in tumor spheroids and alter the microenvironment.
العنوان: | Colorectal cancer-associated anaerobic bacteria proliferate in tumor spheroids and alter the microenvironment. |
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المؤلفون: | Kasper SH; Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA. stephen.kasper@merck.com., Morell-Perez C; Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA., Wyche TP; Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA., Sana TR; Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA., Lieberman LA; Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA., Hett EC; Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA. erik.hett@merck.com. |
المصدر: | Scientific reports [Sci Rep] 2020 Mar 24; Vol. 10 (1), pp. 5321. Date of Electronic Publication: 2020 Mar 24. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
مواضيع طبية MeSH: | Cell Culture Techniques/*methods , Colorectal Neoplasms/*microbiology , Spheroids, Cellular/*metabolism, Bacteria, Anaerobic ; Cell Line, Tumor ; Coculture Techniques/methods ; Colorectal Neoplasms/pathology ; Disease Progression ; Fusobacterium Infections/microbiology ; Fusobacterium nucleatum/genetics ; Fusobacterium nucleatum/metabolism ; Fusobacterium nucleatum/pathogenicity ; Humans ; Models, Biological ; Tumor Microenvironment/physiology |
مستخلص: | Recent reports show that colorectal tumors contain microbiota that are distinct from those that reside in a 'normal' colon environment, and that these microbiota can contribute to cancer progression. Fusobacterium nucleatum is the most commonly observed species in the colorectal tumor microenvironment and reportedly influences disease progression through numerous mechanisms. However, a detailed understanding of the role of this organism in cancer progression is limited, in part due to challenges in maintaining F. nucleatum viability under standard aerobic cell culture conditions. Herein we describe the development of a 3-dimensional (3D) tumor spheroid model that can harbor and promote the growth of anaerobic bacteria. Bacteria-tumor cell interactions and metabolic crosstalk were extensively studied by measuring the kinetics of bacterial growth, cell morphology and lysis, cancer-related gene expression, and metabolomics. We observed that viable F. nucleatum assembles biofilm-like structures in the tumor spheroid microenvironment, whereas heat-killed F. nucleatum is internalized and sequestered in the cancer cells. Lastly, we use the model to co-culture 28 Fusobacterium clinical isolates and demonstrate that the model successfully supports co-culture with diverse fusobacterial species. This bacteria-spheroid co-culture model enables mechanistic investigation of the role of anaerobic bacteria in the tumor microenvironment. |
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تواريخ الأحداث: | Date Created: 20200327 Date Completed: 20210104 Latest Revision: 20210324 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC7093526 |
DOI: | 10.1038/s41598-020-62139-z |
PMID: | 32210258 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2045-2322 |
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DOI: | 10.1038/s41598-020-62139-z |